CN101461834B - Cervus and cucumis polypeptide medicament composition oral preparation and preparation method thereof - Google Patents
Cervus and cucumis polypeptide medicament composition oral preparation and preparation method thereof Download PDFInfo
- Publication number
- CN101461834B CN101461834B CN2009100007921A CN200910000792A CN101461834B CN 101461834 B CN101461834 B CN 101461834B CN 2009100007921 A CN2009100007921 A CN 2009100007921A CN 200910000792 A CN200910000792 A CN 200910000792A CN 101461834 B CN101461834 B CN 101461834B
- Authority
- CN
- China
- Prior art keywords
- cervi
- extracting solution
- filtrating
- cervus
- value
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a method for preparing cervus and cucumis polypeptide medicine composition oral preparation on one hand. The method comprises: firstly, preparing a deer bone extracting solution; secondly, preparing a melon seed extracting solution; and thirdly, combining the deer bone extracting solution and the melon seed extracting solution, and obtaining the cervus and cucumis polypeptide medicine composition oral preparation. The invention also provides a cervus and cucumis polypeptide medicine composition prepared by the method. Compared with the prior method for preparing the cervus and cucumis polypeptide medicine composition oral preparation, the method has the advantages that the method adjusts the pH value when preparing the deer bone extracting solution and the melon seed extracting solution, and removes impurity proteins in the extracting solution through ultrafiltration by an ultrafiltration membrane, so as to guarantee the quality and the safety of products and improve the stability and the treatment effect of the products.
Description
Technical field
The present invention relates to a kind of cervus and cucumis polypeptide drug composition oral preparation and preparation method thereof, relate in particular to a kind of cervus and cucumis polypeptide drug composition oral preparation, belong to biomedicine field.
Background technology
The inorganic elements such as bioactive peptide material and calcium, phosphorus, ferrum that contains multiple bone metabolism in the cervus and cucumis polypeptide pharmaceutical composition; Fructus Melo seed extract and multiple free amino acid etc., its pharmacological action are to regulate bone metabolism and alcium and phosphor metabolization, stimulating osteoblast propagation; Promote new bone formation and regulate calcium, phosphorus metabolism; Increase bone calcium, phosphorus deposition, prevent osteoporosis, have analgesia, antiinflammatory action; Can obviously reduce the permeability of the local blood capillary of fracture, reduce inflammatory exudation, promote local blood circulation, for osteocyte provides a good blood supply environment.The cervus and cucumis polypeptide pharmaceutical composition can be facilitated the osteocyte growth, promotes intermembranous ossification and chondrify, and is remarkable to curative effect of fracture, and multiple bone injury property disease is had significant curative effect.
Domestic patent of invention about the cervus and cucumis polypeptide pharmaceutical composition have be called below 200510108157.7 documents be called below 1,200410013602.7 documents 2 and 02125357.9 below be called documents 3.The method for preparing that documents 1 adopts is that Os Cervi and the hot pressing extraction respectively of Fructus Melo seed, centrifugal, ultrafiltration are prepared from; In this method for distilling; Both do not regulate the Os Cervi extracting liquid pH value, do not regulated the pH value of Fructus Melo seed extracting solution yet, so do not comprised the proteic removal method of impurity in this method.The method for preparing that documents 2 adopts is that Os Cervi is removed impurity albumen, centrifugal, ultrafiltration through hot pressing extraction, soda acid; The Fructus Melo seed through hot pressing extract, centrifugal, ultrafiltration is prepared from; This invention is only removed the impurity albumen that contains in the Os Cervi; Fructus Melo seed extracting solution is not carried out the adjusting of pH value, therefore do not remove the impurity albumen of Fructus Melo seed extracting solution.The method for preparing that documents 3 adopts is that Os Cervi is carried out heating extraction, and hydrochloric acid is regulated the pH value of extracting solution, carry out again freezing static, heated and boiled acid extraction liquid, reuse alkali is regulated filtering supernatant, the freezing static Os Cervi extracting solution that obtains; The method for preparing of this invention Fructus Melo seed extracting solution is identical with the method for preparing of Os Cervi extracting solution, and Os Cervi extracting solution that obtains and the mixing of Fructus Melo seed extracting solution are concentrated, and regulates the pH value of concentrated solution, then carries out ultra-filtration filters, makes the cervus and cucumis polypeptide pharmaceutical composition.When the application inventor found to adopt the method for above-mentioned documents 1 and documents 2 to prepare the cervus and cucumis polypeptide pharmaceutical composition, because impurity protein content wherein is high, the storage life of product was affected; When the method for employing documents 3 prepares the Os Cervi polypeptide pharmaceutical composition, owing to both needed freezing preservation in operation, need heated and boiled again, operational approach is too complicated, the control of pharmaceutical composition difficult quality.
At present; The preparation of cervus and cucumis polypeptide pharmaceutical composition has been widely used in clinical; But find in practice: along with the prolongation of cervus and cucumis polypeptide drug combination preparation storage time; The part finished product has deposition and separates out, thereby has caused visible foreign matters, particulate matter not to meet the regulation of Chinese Pharmacopoeia.This not only influences the quality of medicine, and has brought titanic peril property to clinical practice.The reason that this problem takes place is: the impurity albumen that all contains a large amount of no drug activities in Os Cervi and the Fructus Melo seed; If impurity albumen is not removed the curative effect that not only can influence medicine; And can influence the quality of medicine, thereby can bring titanic peril to clinical practice.Above-mentioned documents 1 and documents 2 are all less than fully impurity albumen being removed.In order to address this problem; Research worker of the present invention is through repeatedly verification experimental verification; Find out a kind ofly can guarantee end product quality, the operational approach of control easily again can be guaranteed simultaneously the cervus and cucumis polypeptide preparation of drug combination method of stability of formulation; Invented simultaneously the cervus and cucumis polypeptide drug composition oral preparation on this basis, thereby a mass is more stable, safer, more effective, the cervus and cucumis polypeptide drug composition oral preparation of taking convenience for extensive patients provides.
Summary of the invention
One aspect of the present invention provides a kind of cervus and cucumis polypeptide drug composition oral preparation, and it has, and long shelf-life, quality stability are good, safe, effective, the advantage of taking convenience.
The present invention provides a kind of said cervus and cucumis polypeptide preparation of drug combination method on the other hand.
One aspect of the present invention provides a kind of method for preparing of cervus and cucumis polypeptide drug composition oral preparation, and this method may further comprise the steps:
1. the preparation of Os Cervi extracting solution:
A. at first Os Cervi is carried out pretreatment;
B. pretreated Os Cervi is pulverized, then added the water for injection of 3-5 times of Os Cervi weight, extracted 3-5 hour down, filter, collect and filtrate at 120-123 ℃, 0.1-0.11MPa pressure;
C. pH value of filtrate is adjusted to 4.5-6.0;
D. the filtrating that will regulate behind the pH value was at room temperature placed 1-4 hour, filtered, and collected filtrating, again filtrating was carried out centrifugalize, collected supernatant I, and the pH value of regulating supernatant I is 10.0-11.0;
E. the supernatant I room temperature that will regulate behind the pH value was placed 1-4 hour, filtered, and collected filtrating, again filtrating was carried out centrifugalize, collected supernatant II, and the pH value of regulating supernatant II be a neutrality;
F. the neutral supernatant II that step e is obtained is 100,000,10,000 and 5000 daltonian ultrafiltration membrance filters through molecular weight successively, collects ultrafiltrate, obtains described Os Cervi extracting solution;
2. the preparation of Fructus Melo seed extracting solution:
G. at first the Fructus Melo seed is carried out pretreatment;
H. pretreated Fructus Melo seed is pulverized, then added the water for injection of 3-5 times of Fructus Melo seed weight, extracted 3-5 hour down, filter, collect and filtrate at 120-123 ℃, 0.1-0.11MPa pressure;
I. repeat above-mentioned steps c-f, obtain described Fructus Melo seed extracting solution;
3. the preparation of cervus and cucumis polypeptide drug composition oral preparation:
J. with described Os Cervi extracting solution and described Fructus Melo seed extracting solution with 1-2: 1 weight ratio merges; Also in merging back Os Cervi extracting solution and described Fructus Melo seed extracting solution, add pharmaceutically acceptable correctives; The adjusting pH value is 4.5-7.5; Use micro-pore-film filtration, collect filtrating, obtain described cervus and cucumis polypeptide drug composition oral preparation.
Preferably; Between described step b and c, also comprise step k; Described step k adds filtering residue weight 3-5 water for injection doubly for filtering to step b in the filtering residue obtain, extracted 3-5 hour filtration down at 120-123 ℃, 0.1-0.11MPa pressure; Collect filtrating I, and the filtrating merging that obtains of will filtrate I and step b.
Preferably, in described step j, described microporous membrane is that the aperture is the microporous membrane of 0.22-0.45 μ m.
More preferably, described microporous membrane is that the aperture is the microporous membrane of 0.22 μ m.
Preferably, in described step f, also ultrafiltrate is used the microporous filter membrane filtration.
Preferably, in the step g among pretreated Fructus Melo seed and the step a weight ratio of pretreated Os Cervi be 0.25-4: 1.
Preferably, in step a, described Os Cervi being carried out pretreatment is at first to remove the connective tissue on the Os Cervi surface of fresh and healthy, then clean Os Cervi; In described step g, the Fructus Melo seed is carried out pretreatment for sophisticated Fructus Melo seed is cleaned.
Preferably, described pharmaceutically acceptable correctives is one or more in sucrose, simple syrup, Mel, rob, sweetleaf centautin, cyclamate, protein sugar, saccharin sodium, sorbitol and the maltose syrup.
Preferably, with hydrochloric acid pH value of filtrate is adjusted to 4.5-6.0 among the step c, the pH value that uses NaOH to regulate supernatant in the steps d is 10.0-11.0.
Preferably, described oral formulations is an oral administration solution.
Preferably, wherein said Os Cervi is the Os Cervi of Cervus nippon Temminck.
Further aspect of the present invention also provides a kind of method for preparing of cervus and cucumis polypeptide drug composition oral preparation, and this method is made up of following steps:
1. the preparation of Os Cervi extracting solution:
A. at first Os Cervi is carried out pretreatment;
B. pretreated Os Cervi is pulverized, then added the water for injection of 3-5 times of Os Cervi weight, extracted 3-5 hour down, filter, collect and filtrate at 120-123 ℃, 0.1-0.11MPa pressure;
C. pH value of filtrate is adjusted to 4.5-6.0;
D. the filtrating that will regulate behind the pH value was at room temperature placed 1-4 hour, filtered, and collected filtrating, again filtrating was carried out centrifugalize, collected supernatant I, and the pH value of regulating supernatant I is 10.0-11.0;
E. the supernatant I room temperature that will regulate behind the pH value was placed 1-4 hour, filtered, and collected filtrating, again filtrating was carried out centrifugalize, collected supernatant II, and the pH value of regulating supernatant II be a neutrality;
F. the neutral supernatant II that step e is obtained is 100,000,10,000 and 5000 daltonian ultrafiltration membrance filters through molecular weight successively, collects ultrafiltrate, obtains described Os Cervi extracting solution;
2. the preparation of Fructus Melo seed extracting solution:
G. at first the Fructus Melo seed is carried out pretreatment;
H. pretreated Fructus Melo seed is pulverized, then added the water for injection of 3-5 times of Fructus Melo seed weight, extracted 3-5 hour down, filter, collect and filtrate at 120-123 ℃, 0.1-0.11MPa pressure;
I. repeat above-mentioned steps c-f, obtain described Fructus Melo seed extracting solution;
3. the preparation of cervus and cucumis polypeptide drug composition oral preparation:
J. with described Os Cervi extracting solution and described Fructus Melo seed extracting solution with 1-2: 1 weight ratio merges; Also in merging back Os Cervi extracting solution and described Fructus Melo seed extracting solution, add pharmaceutically acceptable correctives; The adjusting pH value is 4.5-7.5; Use micro-pore-film filtration, collect filtrating, obtain described cervus and cucumis polypeptide drug composition oral preparation.
Preferably; Between described step b and c, also comprise step k; Described step k adds filtering residue weight 3-5 water for injection doubly for filtering to step b in the filtering residue obtain, extracted 3-5 hour filtration down at 120-123 ℃, 0.1-0.11MPa pressure; Collect filtrating I, and the filtrating merging that obtains of will filtrate I and step b.
Preferably, in described step j, described microporous membrane is that the aperture is the microporous membrane of 0.22-0.45 μ m.
More preferably, described microporous membrane is that the aperture is the microporous membrane of 0.22 μ m.
Preferably, in described step f, also ultrafiltrate is used the microporous filter membrane filtration.
Preferably, in the step g among pretreated Fructus Melo seed and the step a weight ratio of pretreated Os Cervi be 0.25-4: 1.
Preferably, in step a, described Os Cervi being carried out pretreatment is at first to remove the connective tissue on the Os Cervi surface of fresh and healthy, then clean Os Cervi; In described step g, the Fructus Melo seed is carried out pretreatment for sophisticated Fructus Melo seed is cleaned.
Preferably, described pharmaceutically acceptable correctives is one or more in sucrose, simple syrup, Mel, rob, sweetleaf centautin, cyclamate, protein sugar, saccharin sodium, sorbitol and the maltose syrup.
Preferably, with hydrochloric acid pH value of filtrate is adjusted to 4.5-6.0 among the step c, the pH value that uses NaOH to regulate supernatant in the steps d is 10.0-11.0.
Preferably, described oral formulations is an oral solution.
Preferably, wherein said Os Cervi is the Os Cervi of Cervus nippon Temminck.
Further aspect of the present invention provides a kind of cervus and cucumis polypeptide drug composition oral preparation that is prepared from described method.
The invention has the advantages that: 1. when preparation Os Cervi extracting solution and Fructus Melo seed extracting solution, all carried out regulating the operation of pH value in the inventive method, the present invention simultaneously is controlled at pH value in the narrow relatively scope when regulating extracting liquid pH value.This is because the application inventor is surprised to find, and so the purpose of operation is removed the impurity albumen in the extracting solution in the operation of regulating pH value; Keep the useful albumen in the extracting solution simultaneously; Under the prerequisite that keeps cervus and cucumis polypeptide pharmaceutical composition medicinal effects, this pharmaceutical composition storage life is able to prolong, and simultaneously pH value is controlled in this scope; Saved in the prior art follow-up passing through and freezingly staticly removed sedimentary operation with heated and boiled; Both guaranteed product stability, and simplified preparation technology again, preparation technology of the present invention in addition is simple and be convenient to control.Remove the impurity albumen in the extracting solution through this operation, thereby guaranteed the quality of product, increased the stability of product, guaranteed security of products.
2. Os Cervi extracting solution and Fructus Melo seed extracting solution are used molecular weight respectively successively is 100,000,10,000,5000 daltonian ultrafilter membrane ultrafiltration in the present invention; Collected molecular weight less than 5000 daltonian ultrafiltrates; It is better that the ultrafiltrate that has proved this molecular weight ranges through pharmacodynamics test and the solution of other molecular weight ranges are compared medical effect, and the stability of the pharmaceutical composition that is prepared from simultaneously also is better than the solution of other molecular weight ranges.
3. oral formulations preferred oral solution of the present invention is a liquid formulation still, has effect rapidly, eutherapeutic characteristics.Because of unit dose package, so carry, taking convenience.
4. divided dose of the present invention is accurate, and dose is little, and the delicious easy patient of being accepts.The present invention is that aseptic condition is sealed in the oral liquid standard jar, and it is long to have a storage period, steady quality, not perishable characteristics.
The specific embodiment
Further describe the present invention below in conjunction with specific embodiment, advantage of the present invention and characteristics will be more clear along with description.But these embodiment only are exemplary, scope of the present invention are not constituted any restriction.It will be understood by those skilled in the art that and down can make amendment with form or replace without departing from the spirit and scope of the present invention, but these modifications and replacing all fall in protection scope of the present invention the details of technical scheme of the present invention.
Embodiment 1
(1) preparation of Os Cervi extracting solution: get fresh and healthy Os Cervi 20kg, remove the connective tissue on surface, clean, be broken into fritter, add the water for injection of 3 times of weight, i.e. 60kg extracted 3 hours down in 121 ℃, 0.1MPa pressure, filtered, and collected filtrating.To extract residual residue with quadrat method, filter, and collect filtrating I, merge Os Cervi filtrating and filtrating I.Add the 3mol/L hydrochloric acid solution in the solution after merging and regulate pH value to 4.5, at room temperature, placed 1 hour, filter, collect filtrating, again filtrating is carried out centrifugalize, collect supernatant I.Upwards add the 3mol/L sodium hydroxide solution in the clear liquid I and regulate pH value to 10.0, at room temperature, placed 1 hour, filter, collect filtrating, centrifugal, collect supernatant II.The pH value of regulating supernatant II is to neutral, and promptly 7.0, neutral supernatant II is 100,000,10,000,5000 daltonian ultrafilter membrane ultrafiltration through molecular weight respectively successively, collects ultrafiltrate, makes the Os Cervi extracting solution.
(2) preparation of Fructus Melo seed extracting solution: get sophisticated Fructus Melo seed 80kg, clean, be ground into powder, add the water for injection of 3 times of weight, i.e. 240kg extracted 3 hours down in 121 ℃, 0.1MPa pressure, filtered, and collected filtrating.With quadrat method residual residue hot pressing is extracted, filter, collect filtrating I, merge Fructus Melo seed filtrating and filtrating I.Add the 3mol/L hydrochloric acid solution in the solution after merging and regulate pH value to 4.5, at room temperature, placed 1 hour, filter, collect filtrating, centrifugal, collect supernatant I.Upwards add the 3mol/L sodium hydroxide solution in the clear liquid I and regulate pH value to 10.0, placed 1 hour, filter, collect filtrating, centrifugal, collect supernatant II.The pH value of regulating supernatant II is to neutral, and promptly 7.0, neutral solution is 100,000,10,000,5000 daltonian ultrafilter membrane ultrafiltration through molecular weight respectively successively, collects ultrafiltrate, makes Fructus Melo seed extracting solution.
(3) merge Os Cervi extracting solution and Fructus Melo seed extracting solution according to 1: 1 weight ratio; Add suitable amount of sucrose or simple syrup, the pH value of regulator solution is 4.5, with the filtering with microporous membrane of 0.22 μ m; Collect filtrating, make cervus and cucumis polypeptide drug composition oral solution.
Embodiment 2
(1) preparation of Os Cervi extracting solution: get fresh and healthy Os Cervi 50kg, remove the connective tissue on surface, clean, be broken into fritter, add the water for injection of 4 times of weight, i.e. 200kg extracted 4 hours down in 121 ℃, 0.11MPa pressure, filtered, and collected Os Cervi filtrating.Extract residual residue with quadrat method, filter, collect filtrating I, merge Os Cervi filtrating and filtrating I.Add the 4mol/L hydrochloric acid solution in the solution after merging and regulate pH value to 5.0, at room temperature, placed 3 hours, filter, collect filtrating, again filtrating is carried out centrifugalize, collect supernatant I.Upwards add the 4mol/L sodium hydroxide solution in the clear liquid I and regulate pH value to 11.0, at room temperature, placed 3 hours, filter, collect filtrating, centrifugal, collect supernatant II.Regulate the pH value to 7.0 of supernatant II, neutral supernatant II is 100,000,10,000,5000 daltonian ultrafilter membrane ultrafiltration through molecular weight respectively successively, collects ultrafiltrate.Filtrating is collected filtrating with the filtering with microporous membrane of 0.22 μ m, makes the Os Cervi extracting solution.
(2) preparation of Fructus Melo seed extracting solution: get sophisticated Fructus Melo seed 25kg, clean, be ground into the water for injection that powder adds 4 times of weight, i.e. 100kg, 0.11MPa extracted 4 hours under 121 ℃ of pressure, filtered, and collected Fructus Melo seed filtrating.With quadrat method residual residue hot pressing is extracted, filter, collect filtrating I, merge Fructus Melo seed filtrating and filtrating I.Add the 4mol/L hydrochloric acid solution in the solution after merging and regulate pH value to 5.0, at room temperature, placed 3 hours, filter, collect filtrating, centrifugal, collect supernatant I.Upwards add the 4mol/L sodium hydroxide solution in the clear liquid I and regulate pH value to 11.0, at room temperature, placed 3 hours, filter, collect filtrating, centrifugal, collect supernatant II.Regulate the pH value to 7.0 of supernatant II, neutral supernatant is 100,000,10,000,5000 daltonian ultrafilter membrane ultrafiltration through molecular weight respectively successively, collects ultrafiltrate.Filtrating is collected filtrating with the filtering with microporous membrane of 0.22 μ m, makes Fructus Melo seed extracting solution.
(3) merge Os Cervi extracting solution and Fructus Melo seed extracting solution according to 2: 1 ratios; Add suitable amount of sucrose and saccharin sodium; The pH value of regulator solution is 6.0, with the filtering with microporous membrane of 0.22 μ m, collects filtrating; The method for preparing conventional according to oral liquid prepares, and makes cervus and cucumis polypeptide drug composition oral solution.
Embodiment 3
(1) preparation of Os Cervi extracting solution: get fresh and healthy Os Cervi 100kg, remove the connective tissue on surface, clean, be broken into fritter, add the water for injection 500kg of 5 times of weight, extracted 5 hours down, filter, collect Os Cervi filtrating in 121 ℃, 0.11MPa pressure.With quadrat method residual residue hot pressing is extracted, filter, collect filtrating I, merging filtrate I and Os Cervi filtrating.Add the 5mol/L hydrochloric acid solution in the solution after merging and regulate pH value to 6.0, room temperature was placed 4 hours, filtered, and collected filtrating, again filtrating was carried out centrifugalize, collected supernatant I.Upwards add the 5mol/L sodium hydroxide solution in the clear liquid I and regulate pH value to 11.0, room temperature was placed 4 hours, filtered, and collected filtrating, and is centrifugal, collects supernatant II.Regulate the pH value to 7.0 of supernatant II, neutral supernatant II is 100,000,10,000,5000 daltonian ultrafilter membrane ultrafiltration through molecular weight respectively, collects ultrafiltrate.Filtrating is collected filtrating with the filtering with microporous membrane of 0.22 μ m, makes the Os Cervi extracting solution.
(2) preparation of Fructus Melo seed extracting solution: get sophisticated Fructus Melo seed 25kg, clean, be ground into powder, add the water for injection of 5 times of weight, i.e. 125kg extracted 5 hours down in 121 ℃, 0.11MPa pressure, filtered, and collected Fructus Melo seed filtrating.With quadrat method residual residue hot pressing is extracted, filter, collect filtrating I, merge Fructus Melo seed filtrating and filtrating I.Add the 5mol/L hydrochloric acid solution in the solution after merging and regulate pH value to 6.0, room temperature was placed 4 hours, filtered, and collected filtrating, and is centrifugal, collects supernatant I.Upwards add the 5mol/L sodium hydroxide solution in the clear liquid I and regulate pH value to 11.0, placed 4 hours, filter, collect filtrating, centrifugal, collect supernatant II.Regulate the pH value to 7.0 of supernatant II, neutral solution is 100,000,10,000,5000 daltonian ultrafilter membrane ultrafiltration through molecular weight respectively, collects ultrafiltrate.Filtrating is collected filtrating with the filtering with microporous membrane of 0.22 μ m, makes Fructus Melo seed extracting solution.
(3) merge Os Cervi extracting solution and Fructus Melo seed extracting solution according to 4: 1 ratios; Add an amount of sweetleaf centautin or sorbitol; The pH value of regulator solution is 7.5, with the filtering with microporous membrane of 0.22 μ m, collects filtrating; Method for preparing according to the routine of oral liquid prepares, and makes cervus and cucumis polypeptide drug composition oral solution.
Test Example
Stability test:
In order to examine or check the quality stability of the prepared cervus and cucumis polypeptide drug composition oral preparation of the inventive method; Sample is placed by the long term test condition; 25 ℃ of temperature; According to the requirement of two appendix related checks of Chinese Pharmacopoeia version in 2005, investigate the visible foreign matters in the sample and the steadiness of particulate matter in 48 months, concrete outcome is following:
The sample stability result of the test
The result: sample was placed 48 months according to the accelerated test condition, and the visible foreign matters of sample and particulate matter inspection all meet officinal regulation, prove constant product quality of the present invention, and invented technology can be controlled the quality of product.
Pharmacodynamics test:
In order to examine or check the prepared cervus and cucumis polypeptide drug composition oral preparation of the inventive method whether safely, effectively, carried out following pharmacodynamics test, the concrete test as follows:
One, the antiinflammatory action of cervus and cucumis polypeptide drug composition oral preparation research
1. test material
Animal: Wistar rat.
Sample: cervus and cucumis polypeptide oral solution (specification: 2mg/ml)
Aspirin Enteric-coated Tablets
2. test method
The test of rat carrageenan pedal swelling
50 of Wistar rats; Be divided into 5 groups at random according to body weight, i.e. model control group (distilled water), the basic, normal, high dosage of cervus and cucumis polypeptide drug composition oral solution (3.5,7,14mg/kg) group; Positive control drug Aspirin Enteric-coated Tablets (150mg/kg) group, 10 every group.Freshly prepared 1% carrageenin suspension 0.1ml causes inflammation at the right back sufficient plantar subcutaneous injection of rat, then cervus and cucumis polypeptide drug composition oral solution is pressed 5ml/100g to each group rat oral gavage medicine, every day 1 time, continuous 7 days.Behind the last medicine 1h adopt rat paw volumetric measurement appearance to measure to cause scorching before and cause scorching back 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, the right back sufficient sole of the foot volume of 6h rat, and calculate inhibitory rate of intumesce.
3. result of the test
Result of the test sees the following form 1.
Table 1 cervus and cucumis polypeptide oral solution on Carrageenan cause foot swelling rat inhibitory rate of intumesce influence (%, x ± s, n=10)
Compare * P＜0.05 with model group, * * P＜0.01, * * * P＜0.001
Can know by last table; Compare with model control group; Cervus and cucumis polypeptide drug composition oral preparation 3.5mg/kg is causing scorching back 4h; Cervus and cucumis polypeptide oral formulations 7mg/kg is causing scorching back 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, and cervus and cucumis polypeptide oral formulations 14mg/kg 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h after causing inflammation all can significantly suppress the foot swelling (P＜0.05 or P＜0.01) that carrageenin causes.
Two, anxious poison test
Sample: cervus and cucumis polypeptide oral liquid (specification: 2mg/ml)
According to the study of tcm new drug guideline, the cervus and cucumis polypeptide drug composition oral preparation has been carried out the acute toxicity of mouse vein and gastric infusion and observed, because of measuring LD
50So, carry out maximum dosage-feeding and measure.Mouse mainline administration 2 times, accumulated dose is 400mg/kg, is equivalent to 1200 times of clinical human RD (20mg/60kg people/sky), does not find untoward reaction and death; Mouse stomach administration 1 time, dosage is 400mg/kg, is equivalent to 1200 times of clinical human RD (20mg/60kg people/sky), does not find untoward reaction and death.
Conclusion: above result of the test shows, steady quality of the present invention, safe in utilization, effective.
Claims (14)
1. the method for preparing of a cervus and cucumis polypeptide drug composition oral preparation, this method may further comprise the steps:
(1) preparation of Os Cervi extracting solution:
A. at first Os Cervi is carried out pretreatment;
B. pretreated Os Cervi is pulverized, then added the water for injection of 3-5 times of Os Cervi weight, extracted 3-5 hour down, filter, collect and filtrate at 120-123 ℃, 0.1-0.11MPa pressure;
C. pH value of filtrate is adjusted to 4.5-6.0;
D. the filtrating that will regulate behind the pH value was at room temperature placed 1-4 hour, filtered, and collected filtrating, again filtrating was carried out centrifugalize, collected supernatant I, and the pH value of regulating supernatant I is 10.0-11.0;
E. the supernatant I room temperature that will regulate behind the pH value was placed 1-4 hour, filtered, and collected filtrating, again filtrating was carried out centrifugalize, collected supernatant II, and the pH value of regulating supernatant II be a neutrality;
F. the neutral supernatant II that step e is obtained is 100,000,10,000 and 5000 daltonian ultrafiltration membrance filters through molecular weight successively, collects ultrafiltrate, obtains described Os Cervi extracting solution;
(2) preparation of Fructus Melo seed extracting solution:
G. at first the Fructus Melo seed is carried out pretreatment;
H. pretreated Fructus Melo seed is pulverized, then added the water for injection of 3-5 times of Fructus Melo seed weight, extracted 3-5 hour down, filter, collect and filtrate at 120-123 ℃, 0.1-0.11MPa pressure;
I. repeat above-mentioned steps c-f, obtain described Fructus Melo seed extracting solution;
(3) preparation of cervus and cucumis polypeptide drug composition oral preparation:
J. with described Os Cervi extracting solution and described Fructus Melo seed extracting solution with 1-2: 1 weight ratio merges; Also in merging back Os Cervi extracting solution and described Fructus Melo seed extracting solution, add pharmaceutically acceptable correctives; The adjusting pH value is 4.5-7.5; Use micro-pore-film filtration, collect filtrating, obtain described cervus and cucumis polypeptide drug composition oral preparation.
2. method according to claim 1; Wherein between described step b and c, also comprise step k; Described step k adds filtering residue weight 3-5 water for injection doubly for filtering to step b in the filtering residue obtain, extracted 3-5 hour filtration down at 120-123 ℃, 0.1-0.11MPa pressure; Collect filtrating I, and the filtrating merging that obtains of will filtrate I and step b.
3. method according to claim 1 and 2, wherein in described step j, described microporous membrane is that the aperture is the microporous membrane of 0.22-0.45 μ m.
4. method according to claim 1 and 2, wherein, described microporous membrane is that the aperture is the microporous membrane of 0.22 μ m.
5. method according to claim 1 and 2 wherein in described step f, is also used the microporous filter membrane filtration with ultrafiltrate.
6. method according to claim 1 and 2, wherein in the step g among pretreated Fructus Melo seed and the step a weight ratio of pretreated Os Cervi be 0.25-4: 1.
7. method according to claim 1 and 2, wherein in step a, described Os Cervi being carried out pretreatment is at first to remove the connective tissue on the Os Cervi surface of fresh and healthy, then clean Os Cervi; In described step g, the Fructus Melo seed is carried out pretreatment for sophisticated Fructus Melo seed is cleaned.
8. method according to claim 1 and 2, wherein said pharmaceutically acceptable correctives are one or more in sucrose, Mel, sweetleaf centautin, cyclamate, protein sugar, saccharin sodium, sorbitol and the maltose syrup.
9. method according to claim 1 and 2, wherein said pharmaceutically acceptable correctives is a simple syrup.
10. method according to claim 1 and 2, wherein said pharmaceutically acceptable correctives is a rob.
11. method according to claim 1 and 2, the pH value that wherein will merge rear filtrate with hydrochloric acid among the step c is adjusted to 4.5-6.0, and the pH value that uses NaOH to regulate supernatant in the steps d is 10.0-11.0.
12. method according to claim 1 and 2, wherein said oral formulations are oral administration solution.
13. method according to claim 1 and 2, wherein said Os Cervi are the Os Cervi of Cervus nippon Temminck.
14. cervus and cucumis polypeptide drug composition oral preparation that is prepared from claim 1 or 2 described methods.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100007921A CN101461834B (en) | 2009-01-09 | 2009-01-09 | Cervus and cucumis polypeptide medicament composition oral preparation and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100007921A CN101461834B (en) | 2009-01-09 | 2009-01-09 | Cervus and cucumis polypeptide medicament composition oral preparation and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101461834A CN101461834A (en) | 2009-06-24 |
| CN101461834B true CN101461834B (en) | 2012-01-04 |
Family
ID=40802769
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009100007921A Active CN101461834B (en) | 2009-01-09 | 2009-01-09 | Cervus and cucumis polypeptide medicament composition oral preparation and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101461834B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104127473B (en) * | 2014-07-31 | 2017-12-29 | 哈尔滨圣泰生物制药有限公司 | A kind of pharmaceutical composition for treating bone disease and its injection and preparation method |
| CN107988302B (en) * | 2018-01-23 | 2020-11-13 | 吉林省吉诺生物工程有限责任公司 | Preparation method of cervus and cucumis polypeptide and application of cervus and cucumis polypeptide in preparation of food with special medical application |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1742778A (en) * | 2005-10-09 | 2006-03-08 | 黑龙江迪龙制药有限公司 | Cervus and cucumis polypeptide injection composition and preparing method |
| CN1883536A (en) * | 2006-05-31 | 2006-12-27 | 哈尔滨吉尔生物科技有限公司 | Orally administered cervus and cucumis polypeptide composition and preparation method thereof |
-
2009
- 2009-01-09 CN CN2009100007921A patent/CN101461834B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1742778A (en) * | 2005-10-09 | 2006-03-08 | 黑龙江迪龙制药有限公司 | Cervus and cucumis polypeptide injection composition and preparing method |
| CN1883536A (en) * | 2006-05-31 | 2006-12-27 | 哈尔滨吉尔生物科技有限公司 | Orally administered cervus and cucumis polypeptide composition and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101461834A (en) | 2009-06-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101628025B (en) | Pharmaceutical composition containing deer bone extractive and melon seed extract | |
| CN108624495A (en) | A method of preparing the sunflower disk functional activity peptide of drop high lithemia | |
| CN104873546A (en) | Novel propolis soft capsule and preparation method thereof | |
| CN109223637A (en) | Subprostrate sophora herbal mixture toothpaste and preparation method | |
| CN106038670A (en) | Preparation method of Vaccinium dunalianum Wight extract | |
| CN101461834B (en) | Cervus and cucumis polypeptide medicament composition oral preparation and preparation method thereof | |
| AU654365B2 (en) | Stevia extract-containing liquid internal medicine and method of preparing the same | |
| CN107988302B (en) | Preparation method of cervus and cucumis polypeptide and application of cervus and cucumis polypeptide in preparation of food with special medical application | |
| CN104127473B (en) | A kind of pharmaceutical composition for treating bone disease and its injection and preparation method | |
| CN103041366B (en) | Bone peptide composition and preparation method thereof | |
| CN100473388C (en) | Extraction of effective portion of gryllotalpidae for anti-cancers and preparation thereof | |
| CN108096318A (en) | Treat pharmaceutical composition of cardiovascular and cerebrovascular disease and its preparation method and application | |
| CN100336530C (en) | Process for preparing plaster to treat hypertension | |
| CN102302617B (en) | Traditional Chinese medicinal preparation for invigorating stomach, relaxing bowel and reducing blood fat and preparation method thereof | |
| JPH0533690B2 (en) | ||
| CN114848687B (en) | Boletus extract and preparation method and application thereof | |
| KR100522532B1 (en) | Composition for hypoglycemic effect comprising paecilomyces japonica and momordica charantia | |
| CN101897756B (en) | Preparation method of silver yellow medicinal preparation containing polyethylene glycol 12-hydroxy stearate | |
| CN1152701C (en) | Kidney-benefiting and tranquilizing medicine and its prepn | |
| CN101897754B (en) | Preparation method of polyethylene glycol 12-hydroxy stearate-containing danshen root medicament injection preparation | |
| CN101389344A (en) | Synthesized medicament and method for treating HIV | |
| CN107811907A (en) | A kind of body lotion for promoting subcutaneous fat to decompose | |
| JP2003171305A (en) | Ameliorating therapeutic agent for diabetes | |
| CN110772575A (en) | Traditional Chinese medicine preparation for tonifying liver and kidney and blackening beard and hair and preparation method thereof | |
| CN104721180A (en) | Application of valeriana jatamansi Jones part in preparation of N-type calcium channel inhibitor |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20090624 Assignee: Harbin Jier Biotechnology Co., Ltd. Assignor: Harbin Gloria Pharmaceuticals Co., Ltd. Contract record no.: 2014230000172 Denomination of invention: Cervus and cucumis polypeptide medicament composition oral preparation and preparation method thereof Granted publication date: 20120104 License type: Exclusive License Record date: 20140507 |
|
| LICC | Enforcement, change and cancellation of record of contracts on the licence for exploitation of a patent or utility model | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20170522 Address after: 150025, 29 Beijing Road, Limin economic and Technological Development Zone, Heilongjiang, Harbin Patentee after: Harbin Yu Heng Pharmaceutical Co., Ltd. Address before: 150090, 29 Beijing Road, Limin economic and Technological Development Zone, Heilongjiang, Harbin Patentee before: Harbin Gloria Pharmaceuticals Co., Ltd. |